Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  23 KEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFN 102
Cdd:cd20935    1 KEVRAMVGSDVELSCICPEGSRFDLNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFN 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 768019566 103 VTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVA 135
Cdd:cd20935   81 VTPQDEQKFHCLVFSQSLELQKVLEVVVTLHVA 113

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  23 KEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFN 102
Cdd:cd20935    1 KEVRAMVGSDVELSCICPEGSRFDLNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFN 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 768019566 103 VTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVA 135
Cdd:cd20935   81 VTPQDEQKFHCLVFSQSLELQKVLEVVVTLHVA 113

Immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2); The members here are composed of the immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2; also known as B7-DC or CD273). PD-L2 is a cell-surface ligand that competes with PD-L1 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the CD28/B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. PD-L2 has a higher affinity for PD-1 but is expressed at lower levels. PD-L2 interaction with PD-1 suppresses T cell proliferation, cytokine production and cytotoxic activity. PD-L2 is expressed on tumor cells, antigen-presenting cells or APCs (such as macrophages, B cells and dendritic cells), and a variety of other immune and nonimmune cells. Tumor expression of PD-L2 may contribute to tumor evasion of immune destruction by inactivating T cells. Thus, PD-L2 is a negative predictor for prognosis among solid cancer patients.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768019566 149 PSQDELTFTCTSiNGYPRPNVYWINKTdnslldqALQNDTVFLNMRGLYDVVSVLRIARTPSVNIGCCIENVLLQQ 224
Cdd:cd20986    8 PGTGEVQLTCQA-RGYPLAEVSWQNVS-------VPANTSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWNAHMKE 75

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  153 ELTFTCTSINGYPRPNVYWInkTDNSLLDQALQNDTVFLNmRGLYDVVSVLRIARTPSVN 212
Cdd:pfam08205  16 EVVATCSSAGGKPAPRITWY--LDGKPLEAAETSSEQDPE-SGLVTVTSELKLVPSRSDH 72

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  23 KEVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFN 102
Cdd:cd20935    1 KEVRAMVGSDVELSCICPEGSRFDLNDLYVYWQISESETVVTYHLPQNSSLENVDSHYRNRALLSLDSMKQGDFSLRLFN 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 768019566 103 VTPQDEQKFHCLVLSQSLGFQEVLSVEVTLHVA 135
Cdd:cd20935   81 VTPQDEQKFHCLVFSQSLELQKVLEVVVTLHVA 113

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  19 DTQEKEVRAMVGSDVELSCACPEGSrfdlnDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSL 98
Cdd:cd16091    1 AVSEVIVVCLLSEDCILPCSFTPGS-----EVVIHWYKQDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASL 75

                         90
                 ....*....|....*..
gi 768019566  99 RLFNVTPQDEQKFHCLV 115
Cdd:cd16091   76 LLRRVQLQDEGRYKCYT 92

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  25 VRAMVGSDVELSCAC-PEGSrfdLNDVYVYWQTSESKTVVtyHIPQNSslENVDSR----YRNRALMSPAGMLRGDFSLR 99
Cdd:cd05713   10 ILALVGEDAELPCHLsPKMS---AEHMEVRWFRSQFSPVV--HLYRDG--QDQEEEqmpeYRGRTELLKDAIAEGSVALR 82

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768019566 100 LFNVTPQDEQKFHCLVlsQSLGFQEVLSVEvtLHVA 135
Cdd:cd05713   83 IHNVRPSDEGQYTCFF--RSGSFYEEATLE--LKVA 114

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  27 AMVGSDVELSCA-CPEgsrFDLNDVYVYWQTSESKTVVTYHIPQNSSLENVDSRYRNRALMSPAGMLRGDFSLRLFNVTP 105
Cdd:cd20984    9 GNIGEDGILSCTfTPD---IKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQL 85

                         90
                 ....*....|..
gi 768019566 106 QDEQKFHCLVLS 117
Cdd:cd20984   86 TDAGTYLCIISN 97

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  24 EVRAMVGSDVELSCACPEGSRFDLNDVYVYWQTSESKtvVTYHIPQNSS-LENVDSRYRNRALMSpagmlRGDFSLRLFN 102
Cdd:cd16087    2 KIQAYFNETAYLPCQFKNPQNISLSELVVFWQDQKKL--VLYELYLGKEkLDNVNSKYIGRTSFD-----QENWTLQLHN 74

                         90
                 ....*....|...
gi 768019566 103 VTPQDEQKFHCLV 115
Cdd:cd16087   75 VQIKDQGTYQCFI 87

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768019566  18 ADTQEKEVRAMVGSDVELSCACPEGSrfdlNDVYVYWQTSESKtvVTYHIPQNSSLEnvdSRYRNRALMSPagmlrgdFS 97
Cdd:cd20946    2 VPSSQQVVTVVENQEVILSCKTPKKT----SSPRVEWKKLQRD--VTFVVFQNNKIQ---GDYKGRAEILG-------TN 65

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 768019566  98 LRLFNVTPQDEQKFHCLVLSQSlGFQEVLSVEVTLHV 134
Cdd:cd20946   66 ITIKNVTRSDSGKYRCEVSARS-DGQNLGEVTVTLEV 101